title: The conserved clusterin gene is expressed in the developing choroid plexus under the regulation of notch but not IGF signaling in zebrafish.
abstract: Recent genome-wide association studies have implicated the clusterin gene in the etiology of Alzheimer's disease. The expression and function of clusterin in the developing brain, however, is poorly understood. In this study, we have characterized the zebrafish clusterin gene and determined its structural conservation, developmental expression, and physiological regulation. The structure of the zebrafish clusterin gene and protein is similar to its human orthologue. Biochemical assays show that zebrafish Clusterin is a secreted protein that cannot bind IGFs. In adult zebrafish, clusterin mRNA is detected in many tissues. In early development, clusterin mRNA becomes detectable at 12 h postfertilization, and its levels gradually increase thereafter. In situ hybridization analysis indicates that clusterin mRNA is specifically expressed in the developing diencephalic and myelencephalic choroid plexus. Among various stresses tested, heat shock, but not hypoxic or ionic stresses, increases the levels of clusterin mRNA. Inhibition of the IGF-I receptor-mediated signaling or overexpression of IGF ligands did not change clusterin mRNA levels. In comparison, inhibition or targeted knockdown of Notch signaling significantly increased clusterin mRNA expression in choroid plexus. These results suggest that clusterin is a marker of choroid plexus in zebrafish, and its expression in the developing choroid plexus is under the regulation of Notch but not IGF signaling.
authors.affiliation: Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, Michigan 48109, USA. cduan@umich.edu
authors.forename: Shuang
authors.initials: S
authors.lastname: Jiao
authors.forename: Wei
authors.initials: W
authors.lastname: Dai
authors.forename: Ling
authors.initials: L
authors.lastname: Lu
authors.forename: Yunzhang
authors.initials: Y
authors.lastname: Liu
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Zhou
authors.forename: Yun
authors.initials: Y
authors.lastname: Li
authors.forename: Vladimir
authors.initials: V
authors.lastname: Korzh
authors.forename: Cunming
authors.initials: C
authors.lastname: Duan
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D045744:Cell Line, Tumor; D002831:Choroid Plexus / Q000196:embryology / Q000378:metabolism*; D051152:Clusterin / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D005260:Female; D018507:Gene Expression Regulation, Developmental; D055786:Gene Knockout Techniques; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D017403:In Situ Hybridization; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism; D008297:Male; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D010802:Phylogeny; D011743:Pyrimidines / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D017526:Receptor, IGF Type 1 / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D051880:Receptors, Notch / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction / Q000187:drug effects; D015027:Zebrafish / Q000196:embryology / Q000235:genetics* / Q000378:metabolism; D029961:Zebrafish Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D051152:Clusterin; C501177:NVP-AEW541; D011743:Pyrimidines; D011758:Pyrroles; D051880:Receptors, Notch; D029961:Zebrafish Proteins; D049452:Green Fluorescent Proteins; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1